In order to fulfill a life-long dream, I traveled to South Africa to perform post-doctoral research at Groote Schuur Hospital, (University of Cape Town) in the laboratory of Frank Brombacher Ph.D. It was here that we provided the first evidence that interleukin 4-driven alternatively activated macrophages were necessary to suppress microbial-driven intestinal inflammation and immunopathology caused by the human parasitic helminth Schistosoma mansoni (Herbert et al. 2004 Immunity).
Upon returning to the United States, I joined the laboratory of Fred. D. Finkelman M.D. to continue my study of Type 2 dependent effector molecules in host immunity against parasitic worms. In the schistosomiasis model, we demonstrated that interleukin 10 and TGF-beta serve distinct immunoregulatory roles in controlling liver immunopathology (Herbert et al. 2008 Journal of Immunology). We demonstrated that Arginase I (a product of alternatively activated macrophages) counter-regulates TH1/TH17-associated inflammation directed against worm ova within the intestine (Herbert et al. 2010 Journal of Immunology). We also demonstrated that IL-4/IL-13 dependent effects on goblet cells (specialized epithelia) mediated the production of RELM-beta, which limited the ability of gastrointestinal nematode parasites to feed and reside within the host (Herbert et al. 2009 Journal of Experimental Medicine).
As principal investigator, my laboratory has uncovered that the mucosal repair molecule, Trefoil factor 2 initiates Type 2 cytokine production within hookworm-damaged lung tissue (Wills-Karp et al. 2012 Journal of Experimental Medicine). In addition, we are investigating how TGF-beta specifically regulates myeloid cell function to promote the resolution of tissue injury (Rani et al. 2011, Heitmann et al. 2012 ). Ongoing studies are designed to better understand the orchestration of Type 2 inflammation and tissue repair at mucosal surfaces.